How to Implement this Assessment in the Clinical Prac5ce?

5th Interna*onal Symposium on Neuropsychiatry HIV - - - Barcelona, May 24-25th, 2012 Neuropsychological Screening in HIV Infec6on: How to Implement this Assessment in the Clinical Prac5ce? Jose A. Muñoz- Moreno - - - Lluita contra la SIDA Founda:on Germans Trias i Pujol University Hospital - - - Barcelona, Catalonia, Spain

Cogni5ve Disorders in HIV Infec*on

Cogni5ve Disorders in HIV Infec*on HIV Specialization / Infectious Diseases

Cogni5ve Disorders in HIV Infec*on Health Psychology

Cogni5ve Disorders in HIV Infec*on Psychiatry

Cogni5ve Disorders in HIV Infec*on Neuropsychology

Cogni5ve Disorders in HIV Infec*on HIV Specialization / Neuropsychology Infectious Diseases Psychiatry Health Psychology

But... is the rou*ne prac*ce in accordance with these new needs in HIV Infec*on and its management??

Clinical Prac5ce in HIV Infec*on F HIV Physicians F Nurses F Health psychologists F Psychiatrists F Neuropsychologists!

Why to Assess? Which Tools? Which Pa5ents and When Monitoring?

Why to Assess?

Main Reasons þ High incidence and prevalence þ Multiple risk factors associated þ Negative contributions þ Lack of treatment þ Complexity in clinical management!

Prevalence of HIV- Associated NCI

Confirming Data NEUROCOGNITIVE IMPAIRMENT * 100 Percent Impaired 75 50 25 Australia (Cysique, 2004) Italy (Tozzi, 2005) USA - CHARTER (Heaton, 2009) Germany (Arendt, 2010) Catalonia - Spain (Muñoz- Moreno, 2010) 0 CDC- A CDC- B CDC- C Muñoz- Moreno et al, 10th Interna*onal Symposium on Neurovirology, Milan, 2010

Leading to Nega5ve Consequences... G Worse Quality of Life G Interference on Daily Living Ac:vi:es G Worse Adherence to An:retroviral Treatment G More Frequent Virological Failure G Predictor of Higher Death Rates Tozzi et al, 2003 Parsons et al, 2006 Schifi]o et al, 2001 Heaton et al, 2004 Gorman et al, 2009 Hinkin et al, 2004 Applebaum et al, 2009 Woods et al, 2009 Tozzi et al, 2005 Letendre et al, 2010 Ellis et al, 1997 Sevigny et al, 2007 Lescure et al, 2011

Interven5ons NEUROACTIVE ARV DRUGS NON- NEUROACTIVE ARV DRUGS Letendre et al, Enhancing ART for HIV Cogn*ve Disorders, Ann Neurol, 2004 Giancola et al, Neuroac*ve ART Drugs Do Not Influence NC Performance, JAIDS, 2006

Insufficient Although Growing Evidence An*nori, 4 th Mee*ng on HIV and CNS, Rome, 2011

Other ARV- Related Approaches Muñoz- Moreno et al, AIDS Res Hum Retroviruses, 2008 Ellis et al, AIDS, 2011

Other ARV- Related Approaches Muñoz- Moreno et al, J Neurovirol, 2010

ARV Treatment Guidelines! Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents (DHHS). December 2009: http://aidsinfo.nih.gov/contentfiles/ AdultandAdolescentGL.pdf

ARV Treatment Guidelines! Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents (DHHS), March 2012: http://aidsinfo.nih.gov/contentfiles/ AdultandAdolescentGL.pdf

Therapeu5cal Approach

Which Tools?

Comprehensive Ba[eries of Neuropsychological Tests Muñoz- Moreno JA, in Research Focus on Cogni5ve Disorders, NY, 2007

Why Neuropsychological Tes5ng? PROS: - Strongly recommended - Large experience in clinical neuropsychology - Experience in HIV infection - Different areas potentially assessed - Variable tools CONS: - Availability / feasibility - Duration of evaluations

Interna5onal Recommenda5ons F National Institute of Mental Health, 1990 F American Tasks Force, 1991 F UNAIDS, 1997 F Antinori, 2007 F Significant number of reviews and studies recommending

Clinical Neuropsychology In multiple diseases regardless of HIV infection! Pattern of neurocognitive alteration in...: Multiple Sclerosis Schizophrenia Aging Alzheimer's Disease Parkinson's Disease ETC, ETC...

Neuropsychological Tes5ng PROS: - Strongly recommended - Large experience in clinical neuropsychology - Experience in HIV infection - Different areas potentially assessed - Variable tools CONS: - Availability / feasibility - Duration of evaluations

HIV Infec5on - Literature 2010: Neurocognitive + HIV: 357 studies / 75 reviews Neuropsychological + HIV: 1014 studies / 129 reviews Cognitive + HIV: 1934 studies / 357 reviews 2011: Neurocognitive + HIV: 470 studies / 95 reviews Neuropsychological + HIV: 1090 studies / 134 reviews Cognitive + HIV: 2095 studies / 371 reviews 2012: Neurocognitive + HIV: 594 studies / 122 reviews Neuropsychological + HIV: 1165 studies / 140 reviews Cognitive + HIV: 2265 studies / 393 reviews

HIV Infec5on - Literature 2010: Neurocognitive + HIV: 357 studies / 75 reviews Neuropsychological + HIV: 1014 studies / 129 reviews Cognitive + HIV: 1934 studies / 357 reviews 237! - 151! - 331! 2011: Neurocognitive + HIV: 470 studies / 95 reviews Neuropsychological + HIV: 1090 studies / 134 reviews Cognitive + HIV: 2095 studies / 371 reviews 2012: Neurocognitive + HIV: 594 studies / 122 reviews 124! - 75! - 170! Neuropsychological + HIV: 1165 studies / 140 reviews Cognitive + HIV: 2265 studies / 393 reviews

HIV- Associated Cogni5ve Profile - Fronto-subcortical pattern, with altered areas well defined: Attention / Working Memory Executive Functioning Information Processing Speed Verbal Fluency Learning Motor Function Verbal Memory - Maybe has this changed?? Cortical hypothesis: Brew, 2004 Valcour, 2006

Neurocogni5ve Areas and Tests PROCESSING INFORMATION SPEED: MOTOR FUNCTION: VERBAL MEMORY: LEARNING: EXECUTIVE FUNCTIONS: - TMT- A: Trail Making Test - Part A - GPT: Grooved Pegboard Test - CVLT- II: California Verbal Learning Test - II - TMT- B: Trail Making Test - Part B - WCST: Wisconsin Card Sor6ng Test - Stroop's Test

Motor Func5on Grooved Pegboard Test Ma[hews, 1964

Verbal Memory and Learning California Verbal Learning Test - II Delis, 2000

Execu5ve Func5oning Wisconsin Card Sor:ng Test (WCST) Kongs, 1993

Informa5on Processing Speed Trail Making Test - Part A (TMT- A) 15 17 21 20 16 18 19 22 5 4 13 6 14 7 SORTIDA 1 24 8 10 2 3 12 9 11 FI 25 23 Reitan, 1974

Execu5ve Func5oning Trail Making Test - Part B (TMT- B) Reitan, 1974

Execu5ve Func5oning Stroop's Test Golden, 1978

Comprehensive Assessment - Recommendations by Frascati Group, in Antinori et al, Neurology, 2007: Table 1. Criteria for clinical diagnosis of central nervous system disorders in HIV-infected adults and adolescents Table 2. HAND criteria Table 3. Examples of tests Table 4. Guidelines for classifying confounds to HIV-associated neurocognitive disorders

Confounding Factors "Evidence of another etiology, including active CNS opportunistic infection or malignancy, psychiatric disorders (e.g., depressive disorder), active alcohol or substance use, or acute or chronic substance withdrawal, must be sought from history, physical and psychiatric examination, and appropriate laboratory and radiologic investigation (e.g., lumbar puncture, neuroimaging). If another potential etiology (e.g., major depression) is present, it is not the cause of the above cognitive, motor, or behavioral symptoms and signs." Mainly: - Drug abuse - CNS opportunistic infections - Psychatric or emotional disorders

Depression and Anxiety Symptoms - Hospital Anxiety and Depression Scale (HADS): Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983; 67: 361-370. - Beck Depression Inventory (BDI): Beck AT, Rush AJ, Shaw BF, and Emery G: Cognitive Therapy of Depression. Guilford Press, New York, 1979. - State-Trait Anxiety Inventory (STAI): Spielberger CD, Gorsuch RL, and Lushene RE: Manual for the State- Trait Anxiety Inventory. Consulting Psychologists Press, Palo Alto, CA, 1970.

Depression Symptoms Hospital Anxiety and Depression Scale (HADS) - 14 items - 2 scales - 1 total scale Golden, 1978

Depression Symptoms Beck Depression Inventory (BDI) - 21 items - 1 scale - 2 sub-scales Golden, 1978

Anxiety Symptoms State- Trait Anxiety Inventory (STAI) - 20 items - 1 scale Golden, 1978

Limita5ons in HIV Clinical Prac5ce PROS: - Strongly recommended - Large experience in clinical neuropsychology - Experience in HIV infection - Different areas potentially assessed - Variable tools CONS: - Availability / feasibility - Duration of evaluations

Availability and Applicability MAIN LIMITATIONS: - Need of a trained neuropsychologist - Expertise and skills are relevant aspects in the application - Multiple tools - Manipulative tools, as well as variable instructions and correction processes - Duration of assessments! (next section)

Time Required for Neuropsychological Tes5ng - NIMH, 1990: 2 recommendations Extended: 7-9 hours of duration Brief: 1-2 hours of duration - Nowadays... Extended: 2-3 hours of duration Brief:?????

Time Required for Neuropsychological Tes5ng - NIMH, 1990: 2 recommendations Extended: 7-9 hours of duration F Relevance of using Screening Tools! Brief: 1-2 hours of duration - Nowadays... Extended: 2-3 hours of duration

What Do We Know About Screening Tools?

Which Pa6ents? Which Pa5ents and When Monitoring?

Characteris5cs of Pa5ents: Which Predictors? According to biomarkers? According to clinical factors? According to demographic variables? According to emotional variables? According to subjective complaints?

Clinical Factors F High number of clinical factors are associated Some of most representative: F AIDS F CD4 Nadir F Time with HIV F Interruptions of ART F Coinfection with HCV F Virological Failure (in Plasma) F CSF Viral Load * *: Considering availability of lumbar puncture in clinical practice!

Demographic Factors Well identified: F Older Age F Education Level (Cognitive Reserve!) F Employment!

Self- Reported NC Complaints Muñoz-Moreno et al, INS, Helsinki, 2009

Self- Reported NC Complaints 3 patients' patterns according to presence or not of NC complaints: F 1) NC Complaint + Neurocognitive Impairment F 2) NC Complaint + No Neurocognitive Impairment F 3) No NC Complaint + Neurocognitive Impairment!

And When Monitoring?

Similar Findings Muñoz-Moreno et al, CROI, 2010

Clinical Factors As Predictors - Current CD4 cell count ( <123 cells/µl) - Time with HIV ( >2.7 years) *: 75.8% of correct classifica*on

Clinical Factors As Predictors - Nadir CD4 cell count ( <365 cells/µl) - Time on current regimen ( >32.2 months) - Highest viral load ( >4.5 cop/ml) *: 88.4% and 84.9% of correct classifica*on

Monitoring: 6 months Impairment not associated with HIV Pa5ent Approach based on: - NC Complaint - Interference in Func6oning Screening - PAOFI - IADLs - Self- reported Neurocogni5ve Tes5ng Screening Method Impairment associated with HIV: ANI No impairment Impairment No impairment Interven:on

Clinician Approach based on clinical suspicion according to: - Clinical Risk Factors, par:cularly: Interference / Complaints: MND Monitoring: 6 months AIDS CD4 Nadir Time with HIV Interrup6ons of ART Coinfec6on with HCV Virological Failure Neurocogni5ve Tes5ng Impairment No Impairment NO Interference / Complaints: ANI Interven:on *In case of Lumbar Puncture availability: Screening Method CSF Viral Load* - Addi:onal Risk Factors: Aging Educa6on Others Impairment No impairment

Thanks for your a[en5on! Jose A. Muñoz- Moreno www.flsida.org